An efficient method for the cleavage of aziridines using hydroxyl compounds

Article abstract of DOI:10.1016/S0040-4039(00)00686-9

A variety of N-activated aziridines were opened with water, primary, allylic, and propargyl alcohols at rt in high yield using a catalytic amount of Sn(OTf)₂ or BF₃·OEt₂. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4039(00)00686-9

Tetrahedron Letters 41 (2000) 4677±4679
An ecient method for the cleavage of aziridines using
hydroxyl compounds
B. A. Bhanu Prasad, G. Sekar and Vinod K. Singh*
Department of Chemistry, Indian Institute of Technology, Kanpur 208 016, India
Received 10 March 2000; accepted 27 April 2000
Abstract
A variety of N-activated aziridines were opened with water, primary, allylic, and propargyl alcohols at rt in
.
high yield using a catalytic amount of Sn(OTf)2 or BF3 OEt2. # 2000 Elsevier Science Ltd. All rights reserved.
The Lewis acid-induced ring-opening of N-substituted aziridines with several nucleophiles such
as TMSN3, TMSCN, and amines has been very well studied,1 5 but aziridine ring-opening with
hydroxyl compounds, to the best of our knowledge, is unknown. In this communication, we
report our e€orts in this direction where aziridines were cleaved with primary, allylic, and propargyl
.
alcohols at rt in the presence of a catalytic amount of Sn(OTf)2 or BF3 OEt2. We further report
that the cleavage is also e€ected with water.
While working on the Sn(OTf)2-induced cleavage reaction of N-tosyl aziridines with TMSCN
in MeOH as solvent, we discovered that the products were b-amino ethers resulting from an
opening of the aziridines with MeOH. The role of TMSCN in these reactions was ruled out as
they also proceeded in its absence. So, in a typical procedure, a solution of N-tosyl aziridine (1 mmol)
and Sn(OTf)2 (10 mol%) in MeOH (1 mL) was stirred at rt for 1 h. The excess MeOH was
removed and the crude product was chromatographed over silica gel to provide pure b-amino
ether6 in 99% yield (Table 1, entry 1). The trans stereochemistry of the product (entry 1) was
deduced from the coupling constants (J=9, 9 and 3.9 Hz) of the peak at ꢀ 2.86 (CH±OMe) in its
1H NMR spectrum. We carried out this ring-opening reaction with MeOH in the presence of
other Lewis acids such as CuCl2 (24 h, 6% yield), SnCl2 (24 h, 8% yield), FeCl3 (24 h, 32% yield),
LiClO4 (24 h, 10% yield), Cu(OTf)2 (24 h, 3% yield), and AlCl3 (12 h, 35%), but very poor yields
of the product were obtained as indicated. Some other Lewis acids such as ZnI2, ZnCl2, and
CoCl2 failed to give any product (12 h, rt). However, the reaction was very ecient with
.
.
BF3 OEt2 (entry 1). Since both Sn(OTf)2 and BF3 OEt2 turned out to be highly e€ective for the
aziridine opening with MeOH, the reaction was extended to the use of several other hydroxyl
compounds.
* Corresponding author. Fax: 91-512-597436; e-mail: vinodks@iitk.ac.in
0040-4039/00/$ - see front matter # 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)00686-9

4678
Table 1
Cleavage of aziridines with hydroxyl compounds in the presence of a catalytic amount of
a
.
Sn(OTf)2 and BF3 OEt2

4679
Ring-opening of the N-tosyl aziridine with EtOH took longer, but a quantitative yield of the
product was obtained (entry 2). The results of the above reaction with allylic and propargyl
alcohols were similar (entries 3 and 4). Ring-openings of the aziridine with benzyl alcohol and
water were carried out in CH2Cl2 and MeCN and the products were obtained in high yields
(entries 5 and 6). The reaction was then extended to a variety of aziridines with a variety of alcohols
and the results are summarized in Table 1. In the case of the phenyl-substituted N-tosylaziridine
(entries 18 and 19), only a single product was obtained due to internal attack of the alcohols
1
(as con®rmed by H NMR and HPLC). Terminal attack was favoured in the case of the alkyl-
substituted acyclic N-tosylaziridines, although the regioselectivity was not good (entries 20±23).7
.
The aziridine ring-opening reaction with hydroxyl compounds was much faster with BF3 OEt2 in
comparison with Sn(OTf)2. The main drawback of this method is that secondary and tertiary
alcohols failed to open aziridines under the above conditions. It was also observed that N-alkyl
substituted azirdines could not be opened with any of the Lewis acids.
Acknowledgements
V.K.S. thanks DST (Government of India) for the Swarnajayanti Fellowship (1998).
References
1. (a) For a general review of aziridine chemistry, see: Pearson, W. H.; Lian, B. W.; Bergmeier, S. C. In
Comprehensive Heterocylic Chemistry II; Katritzky, A. R.; Rees, C. W.; Scriven, E. F. V., Eds.; Pergamon: New
York, 1996; Vol 1a. (b) Dauben, P.; Dubois, L.; Dau, M. E. T. H.; Dodd, R. H. J. Org. Chem. 1995, 60, 2035. (c)
da Zhang, Z.; Sche€old, R. Helv. Chim. Acta 1993, 76, 2602. (d) Bodenan, J.; Chanet-Ray, J.; Vessiere, R.
Synthesis 1992, 288. (e) Sato, K.; Kozikowski, A. P. Tetrahedron Lett. 1989, 30, 4073. (f) Nakajima, K.; Neya, M.;
Yamada, S.; Okawa, K. Bull. Chem. Soc. Jpn. 1982, 55, 3049.
2. For Cr complex-catalyzed opening of aziridines with TMS azide, see: Leung, W.-H.; Yu, M.-T.; Wu, M.-C.;
Yeung, L.-L. Tetrahedron Lett. 1996, 37, 891.
3. For opening of aziridine with TMSCN in the presence of lanthanoid tricyanides, see: (a) Matsubara, S.; Kodama,
T.; Utimoto, K. Tetrahedron Lett. 1990, 31, 6379. (b) Osborn, H. M. I.; Sweeney, J. B. Synlett 1994, 145.
4. For opening of aziridines with amines in the presence of Lewis acids, see: (a) Sekar, G.; Singh, V. K. J. Org. Chem.
1999, 64, 2537. (b) Meguro, M.; Asao, N.; Yamamoto, Y. Tetrahedron Lett. 1994, 35, 7395. (c). Meguro, M.;
Yamamoto, Y. Heterocycles 1996, 43, 2473.
5. For rearrangement of acylaziridines to oxazolines using orthogonal Lewis acids, see: Ferraris, D.; Drury III, W. J.;
Cox, C.; Lectka, T. J. Org. Chem. 1998, 63, 4568.
6. The amino ether (entry 1) was characterized as follows: white solid, mp 60±62ꢀC; H NMR (CDCl3, 400 MHz) ꢀ
1
1.09 (m, 4H), 1.52 (m, 1H), 1.61 (m, 1H), 1.96 (m, 1H), 2.12 (m, 1H), 2.35 (s, 3 H), 2.78 (ddd, J=9.5, 9.3, 3.4 Hz,
1H), 2.86 (ddd, J=9, 9, 3.9 Hz, 1H), 3.12 (s, 3H), 5.03 (s, 1H), 7.22 (d, J=8.3 Hz, 2H), 7.69 (d, J=8.3 Hz, 2H);
13C NMR (CDCl3, 100 MHz) ꢀ 21.5, 23.4, 23.6, 28.6, 31.0, 55.8, 57.0, 81.3, 127.2, 129.5, 137.3, 143.0; mass (EI, m/z):
283 (M+).
1
7. Ratios of the regioisomers were determined by HPLC and H NMR spectra.